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Evaluation of the protective effects of hesperetin against cisplatin-induced ototoxicity in a rat animal model. 2016

Medine Kara, and Hakan Türkön, and Turan Karaca, and Oğuz Güçlü, and Sema Uysal, and Mehmet Türkyılmaz, and Selim Demirtaş, and Fevzi Sefa Dereköy
Department of Otorhinolaryngology, Canakkale Onsekiz Mart University, Faculty of Medicine, 17060 Canakkale, Turkey. Electronic address: medinekara@gmail.com.

OBJECTIVE We aimed to investigate the effects of hesperetin as a flavanon both histopathologically and immunohistochemically on cochlear apoptosis in a rat model of cisplatin-induced ototoxicity (CIO). The evaluation of the effects of hesperetin on cisplatin-induced hearing loss was performed using distortion product otoacoustic emission (DPOAE). METHODS Twenty-eight wistar albino rats were used in the current study. The rats were randomly divided into four groups with seven rats in each group. Group C was exposed to a single dose of cisplatin (12mg/kg) by intraperitoneal injection. Group CH received intraperitoneally cisplatin (12mg/kg) and hesperetin (20mg/kg). Group H was exposed to hesperetin (20mg/kg) intraperitoneally. The sham group (group S) received normal saline (6cc) intraperitoneally. The measurements of DPOAE and signal-noise ratios (SNR) were performed before the treatment and again on the first and 6 days after administration of the drugs. Rats were sacrificed and cochleae were dissected 10 days after drug administration. The cochlear tissue was assessed in all groups by histopathologic, immunohistochemical and TUNEL assay. In addition, serum oxidative stress markers and antioxidant parameters were analyzed. RESULTS There was a significant difference between the basal value and the sixth day at frequencies 8.4, 9.6 and 9.96 for group C. We also found a significant difference between the first and sixth day at frequencies 7.2, 8.4, 9.6 and 9.96. On the 6th day, there were significant differences between C and S groups at all frequencies except 2.4. We showed a significant difference between C and H groups at frequencies 4.8, 6.0, 8.4, 9.6 and 9.96. There was also a significant difference between C and CH groups at frequencies 2.4, and 3.6. We found lower levels of oxidants and higher levels of antioxidants in CH group as compared to C group. C group had a significantly greater number of TUNEL-positive cells than did S, H and CH groups. The number of TUNEL-positive cells in CH group was higher than in S and H groups. There was a significant difference between the positive PCNA cells of CH group compared to S and H groups in spiral ganglion and stria vascularis. In addition, there were no positive PCNA cells in C group. CONCLUSIONS Hesperetin may prevent ototoxicity by increased antioxidant enzymes and reduced oxidant parameters and protected against apoptosis resulting from a proliferation of cochlear cells in CIO.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007758 Ear, Inner The essential part of the hearing organ consists of two labyrinthine compartments: the bony labyrinthine and the membranous labyrinth. The bony labyrinth is a complex of three interconnecting cavities or spaces (COCHLEA; VESTIBULAR LABYRINTH; and SEMICIRCULAR CANALS) in the TEMPORAL BONE. Within the bony labyrinth lies the membranous labyrinth which is a complex of sacs and tubules (COCHLEAR DUCT; SACCULE AND UTRICLE; and SEMICIRCULAR DUCTS) forming a continuous space enclosed by EPITHELIUM and connective tissue. These spaces are filled with LABYRINTHINE FLUIDS of various compositions. Labyrinth,Bony Labyrinth,Ear, Internal,Inner Ear,Membranous Labyrinth,Bony Labyrinths,Ears, Inner,Ears, Internal,Inner Ears,Internal Ear,Internal Ears,Labyrinth, Bony,Labyrinth, Membranous,Labyrinths,Labyrinths, Bony,Labyrinths, Membranous,Membranous Labyrinths
D008297 Male Males
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D003051 Cochlea The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH. Cochleas
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006569 Hesperidin A flavanone glycoside found in CITRUS fruit peels. 4H-1-Benzopyran-4-one, 7-((6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-, (S)-,Hesperidin 2S,Hesperetin 7-Rhamnoglucoside,Hesperetin-7-Rutinoside,2S, Hesperidin,7-Rhamnoglucoside, Hesperetin,Hesperetin 7 Rhamnoglucoside,Hesperetin 7 Rutinoside
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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